Abstract
Pathogenic and therapeutic concepts of psychiatric disturbances gradually evolved in recent decades from an abnormality of neurotransmission in central nervous system (CNS) to an abnormality of neuronal plasticity. In 1977, a molecular and cellular theory of depression was proposed, according to which, in the pathogenesis of depression disturbances of neuronal plasticity in CNS occur, such as atrophy of hippocampal cells, decrease of expression of neurotrophic hormones and impairment of neurogenesis, resulting from interaction of stress factors and genetic predisposition. Antidepressant drugs counteract these processes by preventing toxic action of hypercotisolemia on hippocampal cells, increasing expression of neurotrophic factors, mainly brain-derived neurotrophic factor (BDNF) and stimulating neurogenesis.
The evidence of neuroprotective properties of mood-normalizing drugs (mainly lithium salts and valproates) which may contribute to the therapeutic activity of these drugs has been accumulated for many years. Such properties may be connected with the effect of these drugs on the processes of intracellular signalling such as phosphatydilinositol system, protein kinase C activity, neuroprotective factor bcl-2 and glycogen synthase kinase 3-beta, as well as stimulation of BDNF expression and neurogenesis. A supposition has been made (mainly for lithium salts) that these drugs may favourably influence neurodegenerative brain diseases.
In recent years, assumptions have also been made that an action on neuronal plasticity may be of importance in the mechanism of therapeutic action of neuroleptic drugs, especially those of second generation. Many studies point on the effect of typical and atypical neuroleptic drugs on different parts of the brain. In the course of long-term administration, new generation neuroleptic drugs exert „sparing” effect on brain structures and may even have a neuroprotective effect. This may be connected with an action of these drugs on a broad spectrum of psychopathological symptoms and with their favourable effect on cognitive functions. Pathogenic and therapeutic concepts of psychiatric disturbances gradually evolved in recent decades from an abnormality of neurotransmission in central nervous system (CNS) to an abnormality of neuronal plasticity. In 1977, a molecular and cellular theory of depression was proposed, according to which, in the pathogenesis of depression disturbances of neuronal plasticity in CNS occur, such as atrophy of hippocampal cells, decrease of expression of neurotrophic hormones and impairment of neurogenesis, resulting from interaction of stress factors and genetic predisposition. Antidepressant drugs counteract these processes by preventing toxic action of hypercotisolemia on hippocampal cells, increasing expression of neurotrophic factors, mainly brain-derived neurotrophic factor (BDNF) and stimulating neurogenesis.
The evidence of neuroprotective properties of mood-normalizing drugs (mainly lithium salts and valproates) which may contribute to the therapeutic activity of these drugs has been accumulated for many years. Such properties may be connected with the effect of these drugs on the processes of intracellular signalling such as phosphatydilinositol system, protein kinase C activity, neuroprotective factor bcl-2 and glycogen synthase kinase 3-beta, as well as stimulation of BDNF expression and neurogenesis. A supposition has been made (mainly for lithium salts) that these drugs may favourably influence neurodegenerative brain diseases.
In recent years, assumptions have also been made that an action on neuronal plasticity may be of importance in the mechanism of therapeutic action of neuroleptic drugs, especially those of second generation. Many studies point on the effect of typical and atypical neuroleptic drugs on different parts of the brain. In the course of long-term administration, new generation neuroleptic drugs exert „sparing” effect on brain structures and may even have a neuroprotective effect. This may be connected with an action of these drugs on a broad spectrum of psychopathological symptoms and with their favourable effect on cognitive functions.